Download Tamsulosin and urinary incontinence

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project

Document related concepts

Adherence management coaching wikipedia, lookup

Transcript
Tamsulosin and urinary incontinence
Introduction
Tamsulosin hydrochloride (Omnic®) is an antagonist of α1-adrenoceptors in the
prostate. Tamsulosin is indicated for the treatment of the signs and symptoms of
benign prostatic hyperplasia (BPH). It is also used off-label for the treatment of
nephrolithiasis in women [1]. Tamsulosin has been approved for the Dutch market
since April 1995 [2].
The symptoms associated with benign prostatic hyperplasia (BPH) are related to
bladder outlet obstruction, which is comprised of two underlying components: static
and dynamic. The static component is related to an increase in prostate size
caused, in part, by a proliferation of smooth muscle cells in the prostatic stroma.
The dynamic component is a function of an increase in smooth muscle tone in the
prostate and bladder neck leading to constriction of the bladder outlet. Smooth
muscle tone is mediated by the sympathetic nervous stimulation of alpha1
adrenoceptors, which are abundant in the prostate, prostatic capsule, prostatic
urethra, and bladder neck. Blockade of these adrenoceptors can cause smooth
muscles in the bladder neck and prostate to relax, resulting in an improvement in
urine flow rate and a reduction in symptoms of BPH. In clinical practice tamsulosin
is also used off-label for the treatment of nephrolithiasis.
Tamsulosin exhibits selectivity for α1-receptors in the human prostate. At least
three discrete α1-adrenoceptor subtypes have been identified: α1A, α1B, and α1D;
their distribution differs between human organs and tissue. Approximately 70% of
the α1-adrenoreceptors in the human prostate are of the α1A subtype [3].
Other selective α1-antagonists for the treatment of BPH on the Dutch market are
alfuzosin (Xatral®), doxazosin (Cardura®), silodosin (Silodyx®) and terazosin
(Hytrin®).
Urinary incontinence often has an identifiable cause in younger persons. In older
persons a multifactorial syndrome is more likely. Neuro-urinary pathology, agerelated factors, comorbid conditions, medications, and functional and cognitive
impairments may play a role in the older population [4].
The current observation describes the association between tamsulosin and urinary
incontinence. No reports for incontinence associated with other α1-adrenoceptor
antagonists were received by Lareb. Therefore, a possible class effect was not
investigated.
Reports
On April 11th 2014, the database of the Netherlands
Pharmacovigilance Centre Lareb contained eleven reports of incontinence
associated with the use of tamsulosin. The reports are listed in table 1.
Table 1. Reports of urinary incontinence associated with the use of tamsulosin
Patient,
Number,
Sex, Age,
Source
Drug, daily dose
Indication for use
A 24881
M, 61-70
years
tamsulosin 0.4mg 1dd
hyperplasia of
prostate
Concomitant
Medication
Netherlands Pharmacovigilance Centre Lareb
October 2014
Suspected
adverse
drug
reaction
Time to
onset,
Action with
drug
outcome
urinary
incontinence,
rash
not reported
unknown
not reported
Pharmacist
B 41722
M, 61-70
years
General
Practitioner
tamsulosin 0.4mg 1dd
not reported
urinary
incontinence
3 days
discontinued
recovered
positive
rechallenge
C 44261
M, 61-70
years
Consumer
tamsulosin 0.4mg 1dd
hyperplasia of
prostate
allopurinol
urinary
incontinence
not reported
unknown
not recovered
D 52650
M, 71
years and
older
Pharmacist
tamsulosin 0.4mg 1dd
hydrochlorothiazide
with quinapril
pyridoxine
calcium
levothyroxine
carbasalate
calcium
folic acid
dihydrotachysterol
urinary
incontinence,
therapeutic
response
unexpected
with drug
substitution
not reported
no change
unknown
E 72129
F, 51-60
years
Pharmacist
tamsulosin 0.4mg 1dd
kidney stone
diclofenac
allopurinol
zopiclone
incontinence
3 days
no change
recovered
positive
rechallenge
F 107476
M, 51-60
years
Pharmacist
tamsulosin 0.4mg 1dd
benign prostatic
hyperplasia
incontinence
of urine
2 months
discontinued
not recovered
G 129137
M, 51-60
years
Consumer
dutasteride/tamsulosin
0,5/0,4mg 1dd
benign prostatic
hyperplasia
Incontinence,
ejaculation
failure
2 months
no change
not recovered
H 145200
F, 51-60
years
Specialist
doctor
tamsulosin 0.4mg 1dd
stone urinary bladder
hydrochlorothiazide
incontinence
of urine
several days
discontinued
recovered
I 147585
M, 61-70
years
Pharmacist
tamsulosin 0.4mg 1dd
benign neoplasm of
prostate
losartan
incontinence,
headache,
tremor,
urticaria,
hot flush,
palpitations,
rhinorrhea
1 day
discontinued
recovered
J 160773
M, 61-70
years
Pharmacist
tamsulosin 0.4mg 1dd
lower abdominal pain
leuprorelin
urinary
incontinence
5 days
discontinued
recovered
K 168760
M, 71
years and
older
Pharmacist
tamsulosin 0.4mg 1dd
benign prostatic
hyperplasia
colecalciferol
urea
mometasone
urinary
incontinence,
fecal
incontinence,
therapeutic
response
unexpected
with drug
substitution
4.5 years
discontinued
recovered
Additional information about the cases is described below:
In case A, the complaints were reported as urge incontinence.
Netherlands Pharmacovigilance Centre Lareb
October 2014
In case B, both a positive de- and rechallenge were reported. Additionally, the
patient ceased his excessive consumption of alcohol (gamma-GT value of 280 U/l)
after starting tamsulosin.
In case C, the patient experienced the complaints related to stress incontinence
(blowing his nose).
In case D, the complaints arose when the patient was switched from capsules to
tablets.
In case E, the patient experienced similar problems in the past.
In case F, the patient had not recovered at the time of reporting, which was 6 days
after withdrawal of tamsulosin.
In case G, the patient switched to separate preparations of dutasteride and
alfuzosin and experienced the same complaints. The patient previously used
tamsulosin without dutasteride and experienced the ejaculation disorder.
Incontinence was not reported for this episode of tamsulosin use.
In case I, the patient was treated with cetirizine for his urticaria, and recovered from
all complaints two days after withdrawal of tamsulosin.
In case J, the patient had a history of prostate cancer for which he underwent
surgery. He previously used tamsulosin without experiencing any complaints.
In case K, the patients switched from the Ranbaxy brand (which he had been using
for approximately 2 years) to the Mylan brand and his complaints disappeared
quickly.
Other sources of information
SmPC
Urinary incontinence is not mentioned in the SmPC of tamsulosin [2].
Literature
Urinary incontinence has been described as an adverse effect in women using
tamsulosin. In a prospective study with 106 patients with voiding dysfunction, three
patients developed de novo stress incontinence and one patient experienced an
aggravation of an existing stress incontinence [5]. Furthermore, a study with α1adrenoceptors other than tamsulosin (prazosin, terazosin and doxazosin) showed
a statistically significant higher percentage of urinary incontinence in patients using
α1-adrenoceptors compared to matched controls [6]. Studies investigating this
association in male patients could not be found.
Databases
Table 2. Reports of (urinary) incontinence with tamsulosin (with or without dutasteride) in the
databases of the Netherlands Pharmacovigilance Centre Lareb and the WHO [7] and Eudravigilance
(EMA) database [8].
Database
Preferred Terms
Number of reports
ROR (95% CI)
Lareb
Urinary incontinence
8
7.2 (3.5 – 14.6)
Incontinence
3
18.3 (5.6 – 59.3)
Total
11
8.7 (4.7 – 15.9)
Urinary incontinence
103
5.1 (4.2 – 6.1)
Incontinence
30
9.3 (6.5 – 13.3)
Total
133
5.7 (4.8 – 6.7)
Urinary incontinence
31
3.5 (2.5 – 5.0)
WHO
Eudravigilance
Netherlands Pharmacovigilance Centre Lareb
October 2014
Database
Preferred Terms
Number of reports
ROR (95% CI)
Incontinence
12
4.5 (2.6 – 8.0)
Total
43
3.8 (2.8 – 5.1)
Prescription data
Table 3. Number of patients using tamsulosin in the Netherlands between 2009 and 2013 [9].
Drug
2009
2010
2011
2012
2013
Tamsulosin
172,950
186,450
194,660
199,250
205,890
Tamsulosine /
dutasteride
-
5,723
19,438
28,787
34,019
Mechanism
Tamsulosin binds selectively and competitively to the postsynaptic α1adrenoreceptors, in particular to the subtype α1A and α1D [2]. It is known that α1adrenergic receptors are present in both the detrusor muscle [10] and the bladder
sphincter [11]. The antagonistic effect of tamsulosin on the α1-adrenergic receptors
of the bladder could therefore theoretically result in both urinary retention and
incontinence, depending on the exact affinity of the drug for each receptor subtype
and their ratios in sphincter and detrusor. A functional urodynamic study however,
showed that tamsulosin had a significant relaxing effect on the resting urethral
tone, suggesting a pharmacological treatment for urinary retention [12]. Urinary
incontinence could therefore be seen as a possible detrimental effect of this
pharmacological mechanism.
Discussion and conclusion
Lareb received eleven cases of urinary incontinence associated with the use of
tamsulosin. The reports concern nine males and two females. In five cases a
positive dechallenge was reported and in two cases a positive rechallenge, which
support the causality of this association. However, there was also one negative
dechallenge. In one case the complaints arose after switching to another brand
and in one case after switching to another formulation (tablets to capsules of the
same brand). This association was disproportionality present in the Lareb, WHO
and Eudravigilance databases, has been described in literature and seems
pharmacologically plausible. In addition to the previously described literature, a
case report of a woman experiencing stress urinary incontinence after starting
doxazosin was found [13]. This case shows similarities with our case C who also
experienced stress incontinence, indicating that the complaints are possibly not
due to confounding by indication (BPH). Although the articles found in the literature
are limited to studies in female patients, our data suggest that male patients could
also experience these symptoms.
Although BPH could be considered as a possible confounder, these patients often
experience overflow incontinence. This is however not mentioned in any of the
described cases. Moreover, in two cases (E,H) this can be ruled out since the
patients are female, whereas two other cases (A,C) specifically mention urge and
stress incontinence respectively. Age however, could be a possible confounding
factor in this association.
Netherlands Pharmacovigilance Centre Lareb
October 2014
 Urinary incontinence should be
mentioned in the SmPC of
tamsulosin
References
1.
van LJ, van Koningsbruggen PJ, Boukes FS, Goudswaard AN. [Summary of the
practice guideline 'Urolithiasis' (first revision) from the Dutch College of General Practitioners].
Ned.Tijdschr.Geneeskd. 2008;152(45):2448-51.
2.
Dutch SPC Omnic®. (version date: 2014, access date: 11-4-2014) http://db.cbgmeb.nl/IB-teksten/h17931.pdf.
3.
US SPC Flomax®. (version date: 2011, access date: 11-4-2014)
http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020579s027lbl.pdf.
4.
UpToDate. UpToDate. (version date: 2012, access date: 11-4-2014)
http://www.uptodate.com/.
5.
Lee KS, Han DH, Lee YS, Choo MS, Yoo TK, Park HJ, Yoon H, Jeong H, Lee SJ, Kim
H, et al. Efficacy and safety of tamsulosin for the treatment of non-neurogenic voiding dysfunction in females: a 8week prospective study. J.Korean Med.Sci. 2010;25(1):117-22.
6.
Marshall HJ, Beevers DG. Alpha-adrenoceptor blocking drugs and female urinary
incontinence: prevalence and reversibility. Br.J.Clin.Pharmacol. 1996;42(4):507-9.
7.
WHO Global Individual Case Safety Reports database (Vigibase). (version date: 2014,
access date: 23-4-2014) https://tools.who-umc.org/webroot/ (access restricted).
8.
Eudravigilance database. (version date: 2014, access date: 23-4-2014)
http://bi.eudra.org (access restricted).
9.
College for Health Insurances. GIP database. (version date: 9-6-2009, access date: 163-2011) http://www.gipdatabank.nl/index.asp?scherm=tabellenFrameSet&infoType=g&tabel=01basis&item=J01FF.
10.
Malloy BJ, Price DT, Price RR, Bienstock AM, Dole MK, Funk BL, Rudner XL,
Richardson CD, Donatucci CF, Schwinn DA. Alpha1-adrenergic receptor subtypes in human detrusor. J.Urol.
1998;160(3 Pt 1):937-43.
11.
KNMP kennisbank. (version date: 2014, access date: 11-4-2014)
http://www.kennisbank.knmp.nl/index.asp#home.
12.
Reitz A, Haferkamp A, Kyburz T, Knapp PA, Wefer B, Schurch B. The effect of
tamsulosin on the resting tone and the contractile behaviour of the female urethra: a functional urodynamic study
in healthy women. Eur.Urol. 2004;46(2):235-40.
13.
Menefee SA, Chesson R, Wall LL. Stress urinary incontinence due to prescription
medications: alpha-blockers and angiotensin converting enzyme inhibitors. Obstet.Gynecol. 1998;91(5 Pt 2):8534.
This signal has been raised on October 2014. It is possible that in the meantime other
information became available. For the latest information, including the official SmPC’s,
please refer to website of the MEB www.cbgmeb.nl/cbg/en/default.htm
The Marketing Authorization Holder of tamsulosin (Astellas) has
informed Lareb on 07-10-2014 of the following: After careful
evaluation of the signal report tamsulosin and urinary
incontinence, the Marketing Authorization Holder, is of the
opinion that there is no sufficient evidence to support a causal
relationship between tamsulosin and urinary incontinence. An
addition of a warning for urinary incontinence to the SmPC is
therefore not warranted, according to Astellas.
Netherlands Pharmacovigilance Centre Lareb
October 2014